Affinage

Showing SURF1 — SHY1 is a alias.

SURF1

Surfeit locus protein 1 · UniProt Q15526

Length
300 aa
Mass
33.3 kDa
Annotated
2026-06-10
89 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SURF1 encodes a cytochrome c oxidase (complex IV)-specific assembly factor required for the biogenesis of the respiratory chain; loss-of-function mutations cause COX deficiency, mapped by complementation rescue in patient fibroblasts (PMID:9843204, PMID:9837813). The protein is imported into mitochondria as a precursor, cleaved of its N-terminal leader peptide to a mature ~30 kDa form, and integrated as an integral inner-membrane protein whose two transmembrane domains are both essential for function (PMID:10556302, PMID:10556303). Functionally, SURF1 acts at an early step of COX assembly, promoting association of MTCO2 with a nascent MTCO1·COX4·COX5A subassembly; in its absence assembly stalls at this intermediate and incomplete, unstable Cox1-containing subcomplexes accumulate (PMID:14607829, PMID:22465034). Work in bacterial orthologs established a direct biochemical basis for this role: Surf1 binds heme a in 1:1 stoichiometry via a conserved histidine, receives heme a by transfer from heme a synthase, and uses a conserved transmembrane tryptophan to discriminate heme a from heme o and orient the cofactor for insertion into COX subunit I (PMID:19625251, PMID:21418525). The yeast ortholog Shy1 couples this assembly role to Cox1 translational feedback regulation through interactions with Mss51 and Cox14 and additionally bridges partially assembled complex IV to the bc1 complex into transitional supercomplexes (PMID:17882259). The COX role is specific: complexes I, II, III and pyruvate dehydrogenase assemble normally in SURF1-deficient cells (PMID:11279059). Pathogenic missense alleles (e.g. G124E, I246T) destabilize the protein and abolish COX rescue, whereas neutral variants retain stability and function (PMID:21470975, PMID:10746561, PMID:16120373). Species differences are notable—human COX assembly is far more dependent on SURF1 than mouse, and Surf1-null mice show only modest respiratory phenotypes alongside altered calcium homeostasis, extended lifespan, and induction of mitochondrial stress and biogenesis responses (PMID:17210671, PMID:24911525, PMID:26804654).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established that the yeast SURF1 ortholog Shy1 is a respiration-required inner mitochondrial membrane protein needed for COX activity, providing the first functional anchor for the gene family.

    Evidence Yeast pet mutant complementation and antibody-based subcellular localization in S. cerevisiae

    PMID:9162072

    Open questions at the time
    • Did not define the molecular step of COX biogenesis affected
    • No direct link to a human disease at this stage
  2. 1998 High

    Identified SURF1 as the human gene whose loss causes COX deficiency, converting an orphan respiratory disorder into a defined molecular lesion.

    Evidence Microcell-mediated chromosome transfer and complementation rescue of respiratory deficiency in patient fibroblasts, with sequencing

    PMID:9837813 PMID:9843204

    Open questions at the time
    • Did not establish protein localization or biochemical activity
    • Assembly step not defined
  3. 1999 High

    Defined SURF1 as an integral inner-membrane protein, imported and processed to a mature 30 kDa form, that acts at an early assembly step before incorporation of subunit II, and showed both transmembrane domains are required.

    Evidence Mitochondrial import assays, carbonate extraction, proteinase K protection, BN-PAGE, and domain-deletion complementation in patient fibroblasts and COS7 cells

    PMID:10556302 PMID:10556303 PMID:10746561

    Open questions at the time
    • Molecular nature of the early step (cofactor vs subunit handling) not resolved
    • Direct interaction partners not identified
  4. 2003 High

    Pinpointed the SURF1-dependent step by showing assembly stalls at an MTCO1·COX4·COX5A subassembly, implicating SURF1 in MTCO2 association.

    Evidence Comparative BN-PAGE of subassemblies across COX10, SCO1, and SURF1 patient fibroblast lines

    PMID:14607829

    Open questions at the time
    • Mechanism by which SURF1 promotes MTCO2 docking not shown
    • Did not address cofactor chemistry
  5. 2007 High

    Connected COX assembly to Cox1 translational regulation by showing Shy1 associates with Mss51/Cox14 and subassembly intermediates and bridges to the bc1 complex, placing SURF1 at the nexus of synthesis and supercomplex formation.

    Evidence Reciprocal Co-IP, mass spectrometry, yeast genetics, and supercomplex detection

    PMID:17882259

    Open questions at the time
    • Whether the translational-feedback role is conserved in human SURF1 not directly tested
    • Stoichiometry of these interactions undefined
  6. 2011 High

    Demonstrated that distinct SURF1 functions map to separate assembly steps, with disease-relevant alleles selectively impairing Cox1 hemylation versus translational feedback coupling.

    Evidence Yeast genetics with G137E and Y344D Shy1 mutants, suppressor screening, pulse-chase BN-PAGE, and copper/heme measurements

    PMID:21470975

    Open questions at the time
    • Mechanistic basis of copper changes not resolved
    • Direct demonstration of dual roles in human cells lacking
  7. 2011 High

    Provided direct biochemical evidence that Surf1 is a heme a binding/transfer protein, establishing its molecular activity in cofactor insertion into COX subunit I.

    Evidence In vitro heme a binding (ITC, redox spectroscopy) and heme transfer from heme a synthase to bacterial Surf1, with mutagenesis of conserved histidine and transmembrane tryptophan

    PMID:19625251 PMID:21418525

    Open questions at the time
    • Shown in bacterial orthologs; direct heme transfer by human SURF1 not reconstituted
    • Coupling of heme delivery to subunit assembly not fully mapped
  8. 2010 Medium

    Placed SURF1 in a wider network of COX assembly factors by identifying suppressors (Coa2, Cox10, Coa4) of a disease-mimicking Shy1 allele and a novel cytochrome c-dependent downstream step.

    Evidence Allele-specific suppressor screen, yeast deletion analysis, COX activity assays, and subcellular fractionation

    PMID:20624914

    Open questions at the time
    • Genetic interactions; direct physical links to SURF1 not all established
    • Human relevance of Coa4 not demonstrated here
  9. 2016 High

    Revealed species-specific dependence on SURF1, showing human COX assembly is far more reliant on SURF1 than mouse and that residual COX is funneled into supercomplexes.

    Evidence 2D BN-PAGE, immunodetection, and pulse-chase metabolic labeling comparing human patient and Surf1-/- mouse fibroblasts/tissues

    PMID:22465034 PMID:26804654

    Open questions at the time
    • Molecular basis of the species difference unknown
    • Whether supercomplex routing is cause or consequence not resolved
  10. 2014 High

    Characterized organismal consequences of SURF1 loss, showing a mild bioenergetic phenotype but altered calcium handling, retrograde stress signaling, and biogenesis induction.

    Evidence Surf1-/- mouse isolated mitochondria assays, blood lactate, treadmill endurance, Ca2+ imaging in neurons, and stress-marker Western blots

    PMID:17210671 PMID:24911525

    Open questions at the time
    • Mechanism linking COX deficiency to Ca2+ homeostasis unresolved
    • Tissue-specific UPRmt/Nrf2 triggers not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether mammalian SURF1 directly delivers heme a to MTCO1 in cells and how this is mechanistically coupled to MTCO2 association and supercomplex routing remains to be reconstituted.
  • No reconstituted human heme a transfer
  • Structural model of SURF1 engaging Cox1 intermediate absent
  • Link between assembly role and Ca2+/lifespan phenotypes unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140104 molecular carrier activity 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
COA1COX14MSS51MTCO1MTCO2
Complex memberships
cytochrome c oxidase (complex IV) assembly intermediate

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase (COX); loss-of-function mutations in SURF1 cause COX deficiency, mapping the gene defect to chromosome 9q34 by microcell-mediated chromosome transfer and complementation of respiratory chain deficiency in patient fibroblasts. Microcell-mediated chromosome transfer, complementation assay in patient fibroblasts, DNA sequence analysis Nature genetics High 9837813 9843204
1997 SHY1 (yeast homolog of SURF1) encodes a mitochondrial inner membrane protein required for respiration and cytochrome c oxidase activity in S. cerevisiae; antibody localization placed Shy1p in the inner mitochondrial membrane. Yeast genetics (pet mutant complementation), antibody-based subcellular fractionation/localization, deletion analysis The Journal of biological chemistry High 9162072
1999 Surf-1 protein (Surf-1p) is imported into mitochondria as a precursor, processed by cleavage of an ~40 amino acid N-terminal leader peptide to yield a mature 30 kDa product; it is localized to and tightly bound to the mitochondrial inner membrane. Loss-of-function mutations result in absence of protein and block COX assembly at an early step, most likely before incorporation of subunit II into the nascent Cox1-containing intermediate. Western blot with anti-HA antibodies, mitochondrial import assay, alkaline carbonate extraction, proteinase K protection assay, blue native 2D gel electrophoresis Human molecular genetics High 10556302
1999 Human Surf-1p is an integral inner mitochondrial membrane protein with an essential role in COX assembly; both transmembrane domains are required for function. FLAG-tagged hSurf1 targeted to mitochondria is imported and processed in a membrane-potential-dependent manner. Deletion of the N-terminal or C-terminal transmembrane domain, or co-expression of the two domains as independent entities, fails to rescue COX activity in patient cells. Epitope-tagged protein expression in COS7 cells, mitochondrial import assay, proteinase K digestion of mitoplasts, alkaline carbonate extraction, complementation assay in patient fibroblasts Human molecular genetics High 10556303
2003 In SURF1-deficient patient fibroblasts, COX assembly stalls at the same stage as in SCO1-deficient cells — at a subassembly containing MTCO1, COX4, and COX5A — pointing to a role for SURF1 in promoting the association of MTCO2 with the MTCO1.COX4.COX5A subassembly. Immunoblot analysis of native gels (BN-PAGE), subassembly detection in patient fibroblasts from COX10, SCO1, and SURF1 mutant lines The Journal of biological chemistry High 14607829
2007 Yeast Shy1 (SURF1 ortholog) promotes complex IV biogenesis by associating with multiple protein modules: it interacts with translational regulators Mss51 and Cox14 (which regulate Cox1 synthesis), and also associates with complex IV subassembly intermediates. Formation of these subcomplexes depends on a novel assembly factor Coa1. Shy1 also links partially assembled complex IV to the bc1 complex to form transitional supercomplexes. This places Shy1 at the nexus of Cox1 translational regulation and complex IV assembly. Co-immunoprecipitation, mass spectrometry, yeast genetic analysis, identification of novel assembly factor Coa1, supercomplex detection The EMBO journal High 17882259
2009 Bacterial Surf1 proteins (Surf1c and Surf1q from Paracoccus denitrificans) bind heme a in a 1:1 stoichiometry with Kd values in the submicromolar range when co-expressed with heme a synthesis enzymes; a conserved histidine residue is critical for heme binding. This supports a direct role for Surf1 in heme a cofactor insertion into COX subunit I. Redox difference spectroscopy, isothermal titration calorimetry, in vivo co-expression in E. coli, site-directed mutagenesis of conserved histidine The Journal of biological chemistry High 19625251
2011 In vitro heme a transfer from purified heme a synthase (CtaA) to Surf1c was demonstrated. Mutation of four strictly conserved residues in the transmembrane region abolished heme binding. A conserved tryptophan in transmembrane helix II (W200 in Surf1c) discriminates between heme a and heme o intermediates and likely coordinates the heme a formyl group, orienting the cofactor for transfer to subunit I of COX. In vitro heme transfer assay, site-directed mutagenesis of transmembrane residues, heme composition analysis of purified protein The FEBS journal High 21418525
2008 In Paracoccus denitrificans, Surf1c and Surf1q function independently for the aa3-type cytochrome c oxidase and the ba3-type quinol oxidase, respectively. Chromosomal deletion of either surf1 gene significantly reduced the corresponding oxidase activity. Analysis of purified COX heme content from Δsurf1 strains indicates Surf1 is involved in an early step of cofactor (heme) insertion into subunit I. Chromosomal gene deletion, oxidase activity assays, heme content analysis of purified cytochrome c oxidase Biochimica et biophysica acta Medium 18582433
2011 In yeast, the Leigh syndrome-associated SURF1 missense mutation G124E (corresponding to G137E in Shy1) results in a non-functional protein that phenocopies shy1Δ cells, impairing Cox1 hemylation and lowering mitochondrial copper. The Y344D Shy1 mutant (corresponding to human Y274D) is stable and localizes correctly but accumulates in a 200 kDa COX assembly intermediate, and in yeast it uncouples Cox1 translational feedback regulation from complex IV assembly, demonstrating a dual role of Shy1 at distinct assembly steps. Yeast genetics, missense mutation introduction, suppressor screen, pulse-chase and assembly intermediate analysis by BN-PAGE, copper measurement Human molecular genetics High 21470975
2010 The Leigh syndrome-associated G137E missense mutation in yeast Shy1 (corresponding to SURF1 G124E) results in a non-functional protein. A genetic screen for allele-specific suppressors of G137E Shy1 identified Coa2, Cox10, and a novel factor Coa4 (a twin CX9C motif IMS protein associated with the inner membrane). Coa4 deletion reduces COX activity without impairing Cox1 maturation, placing Coa4 downstream of the Shy1-stabilized Cox1 intermediate; overexpression of cytochrome c (Cyc1) suppresses coa4Δ, linking Coa4 to a cytochrome c-dependent step in COX assembly. Allele-specific suppressor screen, yeast deletion analysis, COX activity assay, subcellular fractionation Molecular and cellular biology Medium 20624914
2003 In SURF1-null patient fibroblasts, absence of Surf1 protein leads to formation of incomplete COX assembly intermediates (~90–120 kDa) and 70–90% reduction in detergent-solubilized COX activity. In intact cells, COX electron-transport activity was only modestly reduced (13–31%), but was completely inhibited by detergent in patient cells (not controls), indicating instability of incomplete assemblies. Additionally, mitochondrial membrane potential sensitivity to uncoupler was increased 2.4-fold, suggesting impaired H+-pumping of incomplete complexes. Blue native PAGE immunoelectrophoresis, spectrophotometric COX assay, oxygen consumption in whole cells, cytofluorometry of membrane potential Biochimica et biophysica acta Medium 12943968
2004 Cells harboring SURF1 mutations show decreased oxygen affinity of COX: the partial pressure of oxygen at half-maximal respiration (P50) was elevated 2.1-fold in intact coupled cells and 3.3-fold in permeabilized uncoupled cells, indicating that incomplete COX assemblies in SURF1-deficient cells have reduced affinity for oxygen. High-resolution respirometry in intact and digitonin-permeabilized patient fibroblasts, oxygen kinetics measurement American journal of physiology. Cell physiology Medium 15269007
1999 None of several truncated or partially deleted SURF1 constructs could rescue COX activity in Surf-1p null mutant cells, indicating that multiple distinct regions of the protein are all essential for function. Furthermore, SURF1 transcripts are virtually absent in mutant cell lines carrying various loss-of-function mutations, suggesting that these mutations cause severe mRNA instability. Transfection of truncated SURF1 constructs into patient cells, functional complementation assay, Northern blot analysis Human molecular genetics Medium 10556302
2000 Missense mutations G385A (Gly124→Glu, in a strictly conserved residue) and T751C (Ile246→Thr, disrupting a predicted β-sheet conserved in higher eukaryotes) are pathogenic SURF1 mutations causing COX assembly defects. COX activity was restored in patient fibroblasts by retroviral complementation with normal SURF1 cDNA, confirming causality. Sequencing, retroviral vector complementation in patient fibroblasts, COX activity measurement, evolutionary conservation analysis Human genetics Medium 10746561
2007 Surf1 knockout mice (Surf1loxP-/-) show a biochemical and assembly COX defect, but also display markedly prolonged lifespan and complete protection from Ca2+-dependent neurotoxicity induced by kainic acid. Primary neuronal cultures from Surf1-/- mice show markedly reduced rise of cytosolic and mitochondrial Ca2+ and reduced mortality compared to controls, while mitochondrial membrane potential is unchanged, suggesting effects on Ca2+ homeostasis may be at least partly independent of effects on COX assembly. Surf1 knockout mouse model (loxP insertion), kainic acid neurotoxicity model, Ca2+ imaging in primary neuronal cultures, mitochondrial membrane potential measurement, lifespan analysis Human molecular genetics High 17210671
2014 Surf1-/- mice show little or no difference in ROS generation, membrane potential, ATP production, or respiration in isolated mitochondria despite >50% reduction in COX activity; however, blood lactate is elevated and running endurance is reduced. Decreased COX activity is associated with increased markers of mitochondrial biogenesis (PGC-1α, VDAC) in heart and skeletal muscle, with tissue-specific induction of the mitochondrial unfolded protein response (UPRmt) in skeletal muscle and Nrf2 antioxidant pathway induction in heart. Surf1-/- mouse model, isolated mitochondria functional assays (ROS, membrane potential, ATP, respiration), blood lactate measurement, treadmill endurance testing, Western blot for biogenesis/stress markers The Biochemical journal High 24911525
2016 Human SURF1 patient fibroblasts accumulate abundant COX1 assembly intermediates, have low COX monomer content, and preferentially recruit COX into I-III2-IVn supercomplexes, with almost no free COX. In contrast, Surf1-/- mouse fibroblasts show lower levels of COX1 intermediates and milder COX monomer decrease, indicating that COX assembly is much more dependent on SURF1 in humans than in mice, and revealing species-specific differences in COX biogenesis. 2D BN-PAGE/SDS-PAGE, immunodetection, inhibition of mitochondrial proteosynthesis with pulse-chase metabolic labeling in patient and KO mouse fibroblasts and tissues Biochimica et biophysica acta High 26804654
2012 In SURF1 patient fibroblasts, assembled COX is present entirely in supercomplex form (I-III2-IV), and lack of COX causes accumulation of the I-III2 supercomplex. The major COX subassemblies that accumulate due to SURF1 mutations range in size ~85–140 kDa and include Cox1-containing complexes. Up-regulation of respiratory chain complexes I, III, and V (32–54%) and accumulation of free Cox5a subunit represent posttranscriptional compensatory mechanisms in SURF1-deficient cells. BN-PAGE, 2D electrophoresis with WB, whole genome expression profiling, analysis of OXPHOS subunit levels in patient fibroblasts Biochimica et biophysica acta Medium 22465034
1995 CpG methylation abolishes binding of ETS family transcription factors to the Su2 site of the bidirectional SURF1/SURF2 promoter; methylation of a single cytosine at position 3 of the consensus ETS site is sufficient to prevent binding. In contrast, methylation does not affect YY1 binding to the Su1 site. This methylation-sensitive ETS binding contributes to transcriptional repression of SURF1. In vitro DNase I footprinting, gel retardation/EMSA, promoter mutation analysis in vivo, CpG methylation of specific sites Nucleic acids research Medium 7731802
1994 YY1 binds to the Su1 site of the bidirectional SURF-1/SURF-2 promoter and stimulates transcription preferentially in the Surf-1 direction. This was established by gel retardation, methylation interference, antibody supershift, and YY1 overexpression experiments. Gel retardation assay, methylation interference, antibody supershift, YY1 overexpression FEBS letters Medium 8034020
2000 Myc overexpression or activation of a Myc-ER fusion protein activates transcription in the Surf-1 direction, and this response requires a functional YY1 binding site. Overexpression of MAP kinase phosphatase MKP-1 (inhibitor of the MAP kinase cascade) blocks the response of the Surf-1 promoter to serum factors. Together these data place the MAP kinase cascade and the Myc-YY1 interaction in the regulatory pathway controlling Surf-1 promoter activity. Overexpression of Myc, Myc-ER fusion, and MKP-1 in reporter assays; promoter mutation analysis Biochimica et biophysica acta Medium 10858544
2005 Post-transcriptional silencing of the Drosophila melanogaster homolog of SURF1 (CG9943) produces COX-specific deficiency and mitochondrial dysfunction. Ubiquitous knockdown causes larval/pupal lethality with severely altered muscle mitochondria; CNS-restricted knockdown produces viable adults with reduced COX-specific activity, behavioral abnormalities (reduced locomotor speed, impaired optomotor response), and abnormal electroretinograms. UAS-dsRNA transgenic silencing, COX histochemistry, electron microscopy of mitochondria, behavioral and electrophysiological assays Genetics Medium 16172499
2014 Silencing of Surf1 (CG9943) in Drosophila S2R+ cells causes selective loss of COX activity associated with decreased oxygen consumption and respiratory reserve. Larvae show defects in all mitochondrial respiratory chain complexes, while adults show COX-selective impairment, establishing that Surf1 is essential for COX activity and mitochondrial function in Drosophila. Post-transcriptional silencing in S2R+ cells and transgenic Drosophila, complex activity assays, oxygen consumption measurement, Seahorse respirometry The Journal of biological chemistry Medium 25164807
2019 Deletion of the surf1 gene in Corynebacterium glutamicum prevents formation of a functional cytochrome aa3 oxidase and disrupts purification of the bc1-aa3 supercomplex. Surf1 homologs from C. diphtheriae, M. smegmatis, and M. tuberculosis can partially complement the growth defect, establishing Surf1 as a conserved assembly factor for actinobacterial cytochrome aa3 oxidase. Chromosomal surf1 deletion, oxidase activity assays (TMPD oxidation), membrane isolation, supercomplex purification attempt, heterologous complementation Biochimica et biophysica acta. Bioenergetics Medium 31226315
2024 S. pombe Shy1 (SURF1 homolog) physically interacts with structural subunits and assembly factors of complex IV, as well as with Rip1 (a subunit of complex III), suggesting involvement in respiratory chain supercomplex assembly. Shy1 is required for expression of mtDNA-encoded genes. Unlike S. cerevisiae Shy1, deletion of shy1 in S. pombe does not critically disrupt respiratory chain assembly, indicating compensatory mechanisms. Co-immunoprecipitation, BN-PAGE, RT-qPCR of mtDNA-encoded genes, shy1 deletion strain analysis Scientific reports Medium 39289458
2004 The SURF1 missense mutation T737C (I246T) is pathogenic — transfection of T737C-mutated SURF1 into SURF1-deficient cells did not restore normal SURF1 protein stability or COX activity. In contrast, the G604C mutation (D202H) is a neutral variant, as G604C-mutated SURF1 restored SURF1 stability and COX activity upon transfection. Absence of immunologically reactive SURF1 protein is diagnostic of pathogenic missense mutations. Transfection of missense mutant constructs into SURF1-deficient cells, Western blot for SURF1 protein, COX activity measurement Mitochondrion Medium 16120373
2001 Surf1 protein is not implicated in the assembly of respiratory chain complexes I, II, III, or the pyruvate dehydrogenase complex — Western blot analysis in SURF1-deficient patient cells showed normal assembly of these complexes, confirming the COX-specific role of SURF1. Western blot and activity assays for multiple respiratory chain complexes in SURF1 patient fibroblasts The Journal of biological chemistry Medium 11279059

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature genetics 499 9843204
1998 Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. American journal of human genetics 427 9837813
2007 Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice. Human molecular genetics 263 17210671
1997 SHY1, the yeast homolog of the mammalian SURF-1 gene, encodes a mitochondrial protein required for respiration. The Journal of biological chemistry 120 9162072
1999 Characterization of SURF-1 expression and Surf-1p function in normal and disease conditions. Human molecular genetics 119 10556302
2003 Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1. The Journal of biological chemistry 116 14607829
2007 Shy1 couples Cox1 translational regulation to cytochrome c oxidase assembly. The EMBO journal 114 17882259
1999 Expression and functional analysis of SURF1 in Leigh syndrome patients with cytochrome c oxidase deficiency. Human molecular genetics 100 10556303
1999 Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency. Annals of neurology 97 10443880
2014 Complex IV-deficient Surf1(-/-) mice initiate mitochondrial stress responses. The Biochemical journal 93 24911525
2002 MR findings in Leigh syndrome with COX deficiency and SURF-1 mutations. AJNR. American journal of neuroradiology 86 12169463
2005 Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1. The Biochemical journal 83 16083427
1995 CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bi-directional promoter of the Surf-1 and Surf-2 genes. Nucleic acids research 83 7731802
2003 Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice. Human molecular genetics 75 12566387
2001 Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency. Human mutation 72 11317352
1991 The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2 genes. Molecular and cellular biology 70 1996091
2003 Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR. American journal of neuroradiology 64 12812953
2001 A SURF1 gene mutation presenting as isolated leukodystrophy. Annals of neurology 59 11409433
2000 Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients. Human genetics 56 10746561
2009 Surf1, associated with Leigh syndrome in humans, is a heme-binding protein in bacterial oxidase biogenesis. The Journal of biological chemistry 54 19625251
2013 SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology 51 24027061
2003 Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome. Biochimica et biophysica acta 47 12943968
2012 SURF1-associated Leigh syndrome: a case series and novel mutations. Human mutation 40 22488715
2005 Post-transcriptional silencing and functional characterization of the Drosophila melanogaster homolog of human Surf1. Genetics 39 16172499
2004 Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations. American journal of physiology. Cell physiology 38 15269007
1994 The Surf-1 and Surf-2 genes and their essential bidirectional promoter elements are conserved between mouse and human. DNA and cell biology 37 7702754
1999 Sequence conservation from human to prokaryotes of Surf1, a protein involved in cytochrome c oxidase assembly, deficient in Leigh syndrome. FEBS letters 36 10622737
1999 Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency. Human genetics 36 10647889
2010 Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family. Molecular and cellular biology 34 20624914
2009 SURF1 missense mutations promote a mild Leigh phenotype. Clinical genetics 34 19780766
2000 A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy caused by cytochrome c oxidase deficiency. Neuromuscular disorders : NMD 34 10899453
2012 Hypertrophic olivary degeneration on magnetic resonance imaging in mitochondrial syndromes associated with POLG and SURF1 mutations. Journal of neurology 33 22729384
1994 YY1 is involved in the regulation of the bi-directional promoter of the Surf-1 and Surf-2 genes. FEBS letters 32 8034020
2021 Adeno-associated viral vector serotype 9-based gene replacement therapy for SURF1-related Leigh syndrome. Molecular therapy. Methods & clinical development 30 34703839
2003 SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiency. Neurology 30 14557577
2013 Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 29 23838831
2018 SURF1 knockout cloned pigs: Early onset of a severe lethal phenotype. Biochimica et biophysica acta. Molecular basis of disease 28 29601977
2012 Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency caused by SURF1 gene mutations. Biochimica et biophysica acta 28 22465034
2011 Role of Surf1 in heme recruitment for bacterial COX biogenesis. Biochimica et biophysica acta 28 21945856
2008 Two variants of the assembly factor Surf1 target specific terminal oxidases in Paracoccus denitrificans. Biochimica et biophysica acta 28 18582433
2007 Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease. Journal of clinical pathology 28 17908801
2005 Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations. Journal of child neurology 28 16225813
2004 Novel SURF1 mutation in a child with subacute encephalopathy and without the radiological features of Leigh Syndrome. American journal of medical genetics. Part A 26 15214016
2002 A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. Journal of child neurology 26 12026244
2016 Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects. Biochimica et biophysica acta 25 26804654
2016 Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts. Redox biology 25 27208630
2001 New splicing-site mutations in the SURF1 gene in Leigh syndrome patients. The Journal of biological chemistry 24 11279059
2013 Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations. Brain & development 22 24262866
2021 Clinical Diagnosis and Treatment of Leigh Syndrome Based on SURF1: Genotype and Phenotype. Antioxidants (Basel, Switzerland) 21 34943053
2014 Leigh syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing. The Journal of biological chemistry 21 25164807
2020 SURF1 related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkey. Molecular genetics and metabolism reports 20 33134083
2001 Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates. Journal of inherited metabolic disease 20 11804207
2001 A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome c oxidase-deficient leigh syndrome and hypertrichosis. Molecular genetics and metabolism 19 11509016
2011 Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast. Human molecular genetics 17 21470975
2008 High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 17 18583168
2011 Characterization of heme-binding properties of Paracoccus denitrificans Surf1 proteins. The FEBS journal 15 21418525
2012 Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations. Brain & development 14 22410471
2006 Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency. Pediatric neurology 14 16765830
2006 Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation. Neuropediatrics 14 16773507
2023 N-acetylcysteine and cysteamine bitartrate prevent azide-induced neuromuscular decompensation by restoring glutathione balance in two novel surf1-/- zebrafish deletion models of Leigh syndrome. Human molecular genetics 13 36795052
2018 SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences. Gene 13 29933018
2018 Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients. Endocrine regulations 11 29715184
2000 Myc and YY1 mediate activation of the Surf-1 promoter in response to serum growth factors. Biochimica et biophysica acta 11 10858544
2019 Identification of Surf1 as an assembly factor of the cytochrome bc1-aa3 supercomplex of Actinobacteria. Biochimica et biophysica acta. Bioenergetics 9 31226315
2018 Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome. Biochemical and biophysical research communications 9 29481804
2010 Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome. Mitochondrion 8 21167962
2009 Heterogeneity of magnetic resonance imaging in Leigh syndrome with SURF1 gene 604G-->C mutation. Clinical imaging 8 19135921
2002 Three novel SURF-1 mutations in Japanese patients with Leigh syndrome. Pediatric neurology 8 11955926
2002 [A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular genetic study in seven children with Leigh syndrome]. Casopis lekaru ceskych 8 12515039
2023 PKA-Msn2/4-Shy1 cascade controls inhibition of proline utilization under wine fermentation models. Journal of bioscience and bioengineering 6 37940488
2016 Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency. Mitochondrion 6 27756633
2004 Diagnostic difficulties with common SURF1 mutations in patients with cytochrome oxidase-deficient Leigh syndrome. Journal of inherited metabolic disease 6 14970746
2001 SURF1 gene mutations in Polish patients with COX-deficient Leigh syndrome. Journal of applied genetics 6 14564068
2024 Characterization of Shy1, the Schizosaccharomyces pombe homolog of human SURF1. Scientific reports 5 39289458
2024 SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype. American journal of medical genetics. Part A 5 39632678
2021 Dexmedetomidine Reverses Postoperative Spatial Memory Deficit by Targeting Surf1 and Cytochrome c. Neuroscience 5 33895343
2009 SURF-1 gene mutation associated with leukoencephalopathy in a 2-year-old. Journal of child neurology 5 19805825
2010 [Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 4 20436434
2005 [Cytochrome c oxydase-deficient Leigh syndrome with homozygous mutation in SURF1 gene]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 4 15885549
2025 Improved AAV9-based gene therapy design for SURF1-related Leigh syndrome with minimal toxicity. Molecular therapy. Methods & clinical development 3 40893166
2020 Novel p.P298L SURF1 mutation in thiamine deficient Leigh syndrome patients compromises cytochrome c oxidase activity. Mitochondrion 3 32380162
2004 Pathogenicity of missense mutations in SURF1 deficiency inducing the Leigh syndrome. Importance in diagnosis. Mitochondrion 3 16120373
2021 A colorimetric biosensor for ultrasensitive detection of the SURF1 gene based on a dual DNA-induced cascade hybridization reaction. Analytical methods : advancing methods and applications 2 34569567
2020 Facial Dysmorphism, Hirsutism, and Failure to Thrive as Manifestation of Leigh Syndrome in a Child with SURF1 Mutation. Journal of pediatric neurosciences 1 33042241
2016 Data on cytochrome c oxidase assembly in mice and human fibroblasts or tissues induced by SURF1 defect. Data in brief 1 27408912
1997 Transcripts containing the sea urchin retroposon family 1 (SURF1) in embryos of the sea urchin Anthocidaris crassispina. Zoological science 1 9520637
2026 Study on Leigh syndrome caused by SURF1 gene mutations and its mechanisms. Frontiers in neurology 0 42004432
2024 Distinct Imaging Markers of Leigh's Disease Linked to SURF1 Mutation: A Pediatric Case Study. The American journal of case reports 0 39080924
2020 Functional studies of Plasmodium falciparum putative SURF1 in Saccharomyces cerevisiae. Journal of vector borne diseases 0 34856712

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